Stabilized formulation

Abstract

A stabilized pharmaceutical composition of anticancer drug and a solvent like Polyethoxylated castor oil (cremophor) also containing any other suitable solubilizer suitable for human administration like dehydrated alcohol, is disclosed. Compositions prepared using this purified polyethoxylated castor oil enhance the stability of paclitaxel in such compositions.

1. A process for purifying a castor oil derivative, non-ionic solvent comprising the steps of:
 a) forming a solution of said solvent in alcohol and water, with or without aid of heating; 
 b) loading the solution on to a chromatography column packed with reverse phase silica; 
 c) running the chromatography column using de-ionized water as the mobile phase to purify the solvent; 
 d) running the chromatography column using an eluent recovering the purified solvent; and 
 e) evaporating the residual water and the eluent. 
 
     
     
       2. The process according to  claim 1 , wherein the solvent is polyethoxylated castor oil or polyoxyl-35-castor oil. 
     
     
       3. The process according to  claim 1 , wherein the solvent is polyehtoxylated castor oil. 
     
     
       4. The process according to  claim 1 , wherein the alcohol is selected from the group consisting of methanol, ethanol, butanol and isopropanol. 
     
     
       5. The process according to  claim 1 , wherein the alcohol is ethanol. 
     
     
       6. The process according to  claim 1 , wherein the eluent is selected from the group consisting of methanol, ethanol, isopropyl alcohol, acetone, acetonitrile and tetrahydrofuran. 
     
     
       7. The process according to  claim 1 , wherein the eluent is acetone. 
     
     
       8. The process according to  claim 1 , wherein the de-ionized water is HPLC grade. 
     
     
       9. The process according to  claim 1 , wherein in step (a) said solution is a solution of polyethoxylated castor oil, alcohol and water. 
     
     
       10. The process according to  claim 1 , wherein said step of forming said solution comprises mixing about polyethoxylated castor oil, dehydrated ethanol and de-ionized water in a ratio of 10:1:33 w/v/v with or without the aid of heat. 
     
     
       11. The process according to claim ,wherein said step of forming said solution comprises mixing about 300 gm of polyethoxylated castor oil, 30 gm of dehydrated ethanol and one liter of HPLC grade non ionic water with or without the aid of heat. 
     
     
       12. The process according to  claim 1 , wherein said solvent is polyethoxylated castor oil and the step the chromatography column comprises a column of 15×30 cms packed with reverse phase silica of C-8 or C-18 type having a particle size of 30-60μ. 
     
     
       13. The process according to  claim 1 , wherein the step of running the chromatograph to purify the solvent comprises the use of de-ionized water as the mobile phase for 1 to 50 minutes. 
     
     
       14. The process according to  claim 13 , wherein the de-ionized water is HPLC grade. 
     
     
       15. The process according to  claim 1 , wherein the aqueous fractions are discarded. 
     
     
       16. A process for purifying a polyoxyl 35 castor oil solution said solution comprising polyoxyl 35 castor oil, water and an alcohol said process comprising loading the solution on to a chromatography column packed with reverse phase silica and running the chromatograph using de-ionized water as the mobile phase followed by eluting the purified polyoxyl 35 castor oil with methanol, ethanol or acetone evaporating the residual alcohol, water and methanol, ethanol or acetone to obtain purified polyoxyl 35 castor oil adapted to produce, when combined with paclitaxel, a pharmaceutical composition not showing more than 0.3% degradation products of paclitaxel identified as Baccatin III, Ethyl ester side chain of Paclitaxel, 10-Deacetyl paclitaxel, 10-Deacetyl 7-epipaclitaxel and 7-epipaclitaxel, after being stored at 50° C. for 10 days. 
     
     
       17. A process for purifying a polyoxyl 35 castor oil solution said solution comprising polyoxyl 35 castor oil, water and an alcohol said process comprising loading the solution on to a chromatography column packed with reverse phase silica of C-8 or C-18 type having a particle size of 30-60μ and running the chromatograph using de-ionized water (HPLC grade as the mobile phase followed by eluting the purified polyoxyl 35 castor oil with methanol, ethanol or acetone, evaporating the residual alcohol, water and methanol, ethanol or acetone to obtain purified polyoxyl 35 castor oil adapted to produce, when combined with paclitaxel, a pharmaceutical composition not showing more than 0.3% degradation products of paclitaxel identified as Baccatin III, Ethyl ester side chain of Paclitaxel, 10-Deacetyl paclitaxel, 10-Deacetyl 7-epipaclitaxel and 7-epipaclitaxel, after being stored at 50° C. for 10 days. 
     
     
       18. The process according to  claim 17 , wherein the eluent is acetone.